Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid‐based thermosensitive liposomes
Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid‐based thermosensitive liposomes
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DOI：
10.1016/j.ijpharm.2017.11.002
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发表时间：
2017-11
影响因子：
5.8
通讯作者：
Negar Sadeghi;R. Deckers;Burcin Ozbakir;S. Akthar;R. Kok;T. Lammers;G. Storm
中科院分区：
文献类型：
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作者：
Negar Sadeghi;R. Deckers;Burcin Ozbakir;S. Akthar;R. Kok;T. Lammers;G. Storm
快速高温（即 39-42°C）触发肿瘤血管系统中含溶血脂的热敏脂质体 (LTSL) 释放阿霉素，已被证明可显着提高临床前肿瘤模型中受热肿瘤组织中的生物可利用药物水平。然而，在 37°C 的温度下，阿霉素也会大量渗漏到血液中，从而降低了 LTSL 的效率，并增加了全身毒性的风险。在传统的脂质体中，胆固醇被掺入双层中以增加脂质体的稳定性。在此，我们研究了胆固醇包合物在 37°C 和高温下对 LTSL 的阿霉素释放特性的影响。为此，制备了三种含有 0、5 和 10mol% 胆固醇的 LTSL 制剂。胆固醇的加入减少了 Hepes 缓冲盐水 (HBS) 以及胎牛血清 (FBS) 中 37°C 下阿霉素的不良渗漏。 LTSL 双层中胆固醇的掺入不影响 LTSL 的高热触发释放特性。这些结果得到了 DSC 测量的支持。因此，总而言之，我们的数据表明，LTSL 中的胆固醇含量为解决阿霉素在 37°C 的血液中从 LTSL 中大量渗漏的问题提供了一个简单的解决方案。
Fast hyperthermia (i.e. 39–42 °C) triggered doxorubicin release from lysolipid-containing thermosensitive liposomes (LTSL) in the tumor vasculature has been demonstrated to result in considerable enhancement of bioavailable drug levels in heated tumor tissue in preclinical tumor models. However, there is also significant leakage of doxorubicin already at 37 °C in the bloodstream, making these LTSL less efficient and increasing the risk for systemic toxicity. In conventional liposomes, cholesterol is incorporated in the bilayer to increase the stability of the liposomes. Here, we investigate the effect of cholesterol inclusion on the doxorubicin release characteristics of LTSL at 37 °C and hyperthermic temperatures.For this purpose, three LTSL formulations with 0, 5 and 10 mol% cholesterol were prepared. Inclusion of cholesterol reduced the undesired doxorubicin leakage at 37 °C in Hepes-buffered saline (HBS) as well as in fetal bovine serum (FBS). The incorporation of cholesterol in the LTSL bilayers did not influence the hyperthermia-triggered release property of the LTSL. These results were supported by DSC measurements.Therefore, in conclusion, our data indicate that cholesterol inclusion in LTSL offers a simple solution to the problem of significant leakage of doxorubicin from LTSL already at 37 °C in the bloodstream.